May 26, 2020

Will Little Subscribe

COVID-19 Science Logbook (Jan-May, 2020)


This logbook is where I recorded my notes on COVID-19 from January 2020 through May 2020. For future posts on COVID-19 and/or SARS-CoV-2, follow my “COVID-19” topic on my subscribe page here.

Those articles can be viewed on my COVID-19 topic page here.

For an interesting historical read, scroll to the bottom and work your way up (this captures the more real-time thinking of our world community during this time).

The below content informed my latest updates to the comprehensive article: Coronavirus Disease 2019 (COVID-19): Understanding the epidemiology, biochemistry, and cognitive biases regarding the spread of — and our reaction to — SARS-CoV-2

May 26, 2020

  • PBS/NOVA have published an excellent hour-long documentary on the virus and its biology/epidemiology here.

May 23-25, 2020

  • And helpful commentary, Q&A on Reddit here.

May 20-22, 2020

  • “It’s led to lots of questions about how we treat patients these days,” Bonow says. “When a 75-year-old man comes in with chest pain, is it a heart attack or COVID?”

May 15-19, 2020

  • “Here we describe multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of an individual who was infected with SARS-CoV in 2003. One antibody, named S309, potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 by engaging the S receptor-binding domain.”
  • Rhonda Patrick discusses COVID-19 at length on the Joe Rogan podcast here. They talk about VitD/VitC, sauna use, blood type nuances w/ SARS-CoV-2 (e.g. type O blood types are better protected).  Long story short - take your Vitamin D supplements and keep stress low + sleep up + exercise up.  (And consider daily sauna use if you can)

May 11-15, 2020

  • From https://www.pnas.org/content/early/2020/05/12/2006874117
  • Speech droplets generated by asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are increasingly considered to be a likely mode of disease transmission. Highly sensitive laser light scattering observations have revealed that loud speech can emit thousands of oral fluid droplets per second. In a closed, stagnant air environment, they disappear from the window of view with time constants in the range of 8 to 14 min, which corresponds to droplet nuclei of ca. 4 μm diameter, or 12- to 21-μm droplets prior to dehydration. These observations confirm that there is a substantial probability that normal speaking causes airborne virus transmission in confined environments.

May 7-10, 2020

  • Eight ways in which scientists hope to provide immunity to SARS-CoV-2 .

May 5-6, 2020

  • “works in a single test tube and does not require the many specialty chemicals, or reagents, whose shortage has hampered the rollout of widespread Covid-19 testing in the U.S. It takes about an hour to get results, requires minimal handling, and in preliminary studies has been highly accurate,”
  • “The children in New York, ages 2 to 15, had high fevers and elevated levels of inflammatory markers, signs that are common in shock and an acute pediatric heart condition called Kawasaki disease, the city’s health department said Monday. The patients, who were hospitalized from April 17 to May 1, also showed symptoms including rash, abdominal pain, vomiting, and diarrhea. Five of the children had to be placed on ventilators; none have died.”
  • Two new studies offer compelling evidence that children can transmit the virus. Neither proved it, but the evidence was strong enough to suggest that schools should be kept closed for now, many epidemiologists who were not involved in the research said.

May 4, 2020

  • “A cohort of 7,336 COVID-19 patients with or without diabetes was retrospectively studied
  • Diabetes status increased the need for medical interventions during COVID-19
  • Diabetes status increased the mortality risk of patients with COVID-19
  • Well-controlled blood glucose correlated with improved outcomes in infected patients”

April 30-May 3, 2020

  • “Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection”
  • “Co-19 shows a difference in fatality rate between males (2.8%) and females (1.7%)33. As ACE2 is located on the X chromosome, there may be alleles that confer resistance to COVID-19, explaining the lower fatality rate in females. Alternatively, the oestrogen and testosterone sex hormones have different immunoregulatory functions, which could influence immune protection or disease severity”
  • “children tend not to develop severe disease despite being capable of experiencing high viral titres”
  • “Controlling the inflammatory response may be as important as targeting the virus”

April 29, 2020

  • The preliminary data showed that the time to recovery was 11 days on remdesivir compared to 15 days for placebo, a 31% decrease. The mortality rate for the remdesivir group was 8%, compared to 11.6% for the placebo group; that mortality difference was not statistically significant.

April 26-28, 2020

  • Not great news for Kevzara as a treatment for preventing cytokine storms.

April 24-25, 2020

  • Not enough data points in this first study it looks like
  • Not promising news; but still too early to tell re: broad implications
  • Many popular-level outlets covered this news, e.g.

April 22-23, 2020

  • “Right now, we have no evidence that the use of a serologic test can show that an individual is immune or is protected from reinfection,” the WHO’s Maria Van Kerkhove said at a briefing last week.
  • Scientists in Europe have pointed to strong antibody production in patients within a few weeks of infection. One study found that people were generally quick to form antibodies, which could help explain why the majority of people do not develop severe cases of Covid-19….But one preprint released this month complicated the landscape.
  • The study will be a randomized, double-blind placebo-controlled study, the medical gold standard in which patients will be assigned one of three options: hydroxychloroquine, the combination of hydroxychloroquine and the antibiotic azithromycin, or placebo.
  • The study will not include patients who are very sick and on ventilators. It will include adults who are hospitalized and are in what doctors call the moderate-to-severe population, for instance, those who need oxygen supplementation.
  • Patients will receive a loading dose of 600 milligrams of hydroxychloroquine, and then 200 mg three times a day. Tsai said that there is “a tight window” to get levels of the drug high enough that they might have antiviral activity without causing too many side effects, such as changes in heart rhythm that the drug can cause. The study will be conducted at more than a dozen sites in the U.S. and will begin within the next few weeks.

April 21, 2020

  • “In this study, we found no evidence that use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with Covid-19. An association of increased overall mortality was identified in patients treated with hydroxychloroquine alone. These findings highlight the importance of awaiting the results of ongoing prospective, randomized, controlled studies before widespread adoption of these drugs.”

April 19-20, 2020

  • Town of 3275 people in Italy went in lock-down super early.  The vast majority of the town was tested two times (14 days apart, starting right after the lock-down).
  • 73 found positive first time. 29 the second time (w/ 8 new cases).  35 out of the 81 people (43.2%) who tested positive showed no symptoms. Viral load similar for all 81 people. No kids had active infections.
  • Implications: this confirms more recent reports showing data closer to 50% asymptomatic (among those infected).  That's good news for the general population, but bad news for the most vulnerable.

April 18, 2020

  • Very practical advice on how to live your life, washing clothes, wiping down packages, etc…
  • “Humans don’t usually move fast enough for this to happen,” Dr. Marr continued. “As we move, we push air out of the way, and most of the droplets and particles get pushed out of the way, too. Someone would have to spray large droplets through talking — a spit talker — coughing or sneezing for them to land on our clothes. The droplets have to be large enough that they don’t follow the streamlines.”

April 16-17, 2020

  • “An early look at the Gilead Sciences trial testing remdesivir for Covid-19 has revealed that the drug seems to be helping severely ill patients rapidly recover from fever and respiratory symptoms, and nearly all patients who were given the drug at a Chicago hospital had been discharged from the hospital in less than a week.“
  • “The scans detect hazy, patchy, “ground glass” white spots in the lung, a telltale sign of Covid-19. In one recent study of 1,014 patients, published in the journal Radiology, scientists in China reported that chest CT found 97% of Covid-19 infections. In comparison, the study found that 48% of patients who had negative results on the swab test, which detect the coronavirus’s genome, in fact had the disease.”
  • “Once you’re a couple of days into infection, chest CT scans don’t miss,” said an emergency medicine physician in Louisiana who asked not to named. With the swab test missing 30% to 50% of cases, physicians in China called for the diagnostic use of CT early in the outbreak there, and “fever clinics” set up in Wuhan and elsewhere began routinely using them.
  • “Doctors treating the sickest Covid-19 patients have zeroed in on a new phenomenon: Some people have developed widespread blood clots, their lungs peppered with tiny blockages that prevent oxygen from pumping into the bloodstream and body.”
  • “A number of doctors are now trying to blast those clots with tPA, or tissue plasminogen activator, an antithrombotic drug typically reserved for treating strokes and heart attacks. Other doctors are eyeing the blood thinner heparin as a potential way to prevent clotting before it starts.”

April 15, 2020

  • “Researchers in Australia and the Netherlands are testing the idea that the vaccine, known as BCG — short for bacille Calmette-Guérin — could have broad power to boost the immune system against the novel coronavirus. In the United States, a research group in Boston hopes to test the vaccine in frontline health workers for the same purpose.”
  • “...prolonged or intermittent social distancing may be necessary into 2022. Additional interventions, including expanded critical care capacity and an effective therapeutic, would improve the success of intermittent distancing and hasten the acquisition of herd immunity. Longitudinal serological studies are urgently needed to determine the extent and duration of immunity to SARS-CoV-2. Even in the event of apparent elimination, SARS-CoV-2 surveillance should be maintained since a resurgence in contagion could be possible as late as 2024.”

April 12-14, 2020

  • Google and Apple have joined forces to alert us when we’ve come in contact with someone who has had COVID-19. (ref)
  • “Essentially, Apple and Google have built an automated contact-tracing system. It’s different from conventional contact-tracing, and probably most useful when combined with conventional methods. Most importantly, it can operate at a far greater scale than conventional contact tracing, which will be necessary given how far the outbreak has spread in most countries. Because it’s coming from Apple and Google, some of this functionality will also eventually be built in to Android and iPhones at an OS-level. That makes this technical solution potentially available to more than three billion phones around the world — something that would be impossible otherwise.”

April 11, 2020

  • From Dr. Rhona Patrick’s newsletter from yesterday:
  • “Subgroups of children could be at greater risk of COVID-19, especially those who are younger, have respiratory problems, or are immunocompromised.” (ref)
  • “Some COVID-19 patients report loss of smell and taste, potentially signaling SARS-CoV2 infiltration of the central nervous system.” (ref)
  • “Treatment with intravenous vitamin C reduced death rates in patients with sepsis and severe acute respiratory failure.”(ref)
  • “Normally, ACE2 is found on lung, kidney, heart, and gut cells. But scientists recently found ACE2 receptors on the cells in peoples’ noses — an “aha” moment for people like Farzen who had studied the 2003-era SARS virus.”
  • “Farzan, a virologist at the Scripps Research Institute’s Florida campus, and other experts believe treatments targeting ACE2, or angiotensin converting enzyme-2, could be the key to unlocking either a coronavirus vaccine or a treatment for Covid-19. The work targeting the receptor is one pathway among dozens that biotech and pharmaceutical companies are exploring as they race to find drugs that could help bring the pandemic under control.”

April 7-10, 2020

  • “The REMAP-CAP study seeks to turn frenetic attempts to save lives on the front lines into a running international experiment, with the goal of quickly identifying optimal treatments for desperately ill patients. By analyzing data on outcomes from more than 50 hospitals, organizers hope to supply fast answers to pressing questions, such as whether the antimalarial drug hydroxychloroquine is an effective therapy and, if so, for which types of patients. The trial will also allow the researchers to test multiple therapies at once.”
  • “Within a period of a week or so, we are going to have a relatively large number of tests available,” Dr. Anthony S. Fauci, the government’s top infectious disease expert, said Friday morning on CNN.

April 4-6, 2020

  • “NextTrace therefore plans to build a decentralized reporting system in which anyone with confirmed Covid-19 can choose to register, anonymously, on an online platform. The platform will use cellphone location and proximity data from cellphones, for people who have opted in, to find individuals who might have been exposed to this case and advise them to be tested. The system would build a contact history for each case.”

April 3rd, 2020

April 2nd, 2020

  • Questions/topics
  • Is taking Advil ok? I’ve heard conflicting reports… sounds like early reports of this being harmful were rumors?
  • Finger prick tests in the UK coming soon (we really need to get a sense for how many people have already been infected without knowing it)
  • Does blood type really make a difference in COVID-19 ?  (looks like yes; “A” higher risk, “O” lower risk)
  • From a data science perspective, this is fascinating (looking at 15 million anonymous cell phone users in the US and who was actually traveling or not)

March 31st & April 1st, 2020

  • NY Times has published detailed case maps by state here.
  • Tocilizumab now on the scene to prevent cytokine storms
  • HCQ for mild cases seems to be key (i.e. not as effective for later-stages)
  • “Some good news in drug trials: A small study of 62 patients in China with mild cases showed promising results for the malaria drug hydroxychloroquine: patients who received it seemed to get over their symptoms faster.” (ref)
  • “The model is meant to be used in patients who are hospitalized, but not yet in the ICU. It analyzes patients’ data — including their vital signs, lab test results, medications, and medical history — and spits out a score on a scale from 0 to 100, with a higher number signaling elevated concern that the patient’s condition is deteriorating.”
  • “Patient 31 was what is known as a super-spreader – someone who passes the infection on to a larger number of people.”
  • Uh oh:
  • “In the days before her diagnosis, she travelled to crowded spots in the city of Daegu and the capital, Seoul. She was then involved in a minor traffic accident and checked into hospital, and while a patient there she attended church services on two occasions and went for lunch in a hotel with a friend, despite developing a fever. In just a few days after she was diagnosed with the coronavirus, hundreds of people at the church she had attended and in the surrounding areas tested positive.”

March 29th & 30th, 2020

  • There are many new drugs now being tested.
  • “Structural basis of receptor recognition by SARS-CoV-2” (Nature)

 

March 27th & 28th, 2020

  • 93% of the 175 deaths in WA thus far have been from people 60 or older, even though the percent of cases is more evenly distributed for people over 20
  • How do these numbers compare to NYC, for example?

March 26th, 2020

  • To state the obvious, the key thing to look for is flattening curves in the coming weeks to see how well the social isolation measures are working, especially in states like New York with large urban areas.

March 24th & 25th, 2020

  • Regarding Remdesivir
  • One of the best data tracking sites I’ve seen:

  • All 30 people got better and there weren’t any obvious differences between the control group and the HCQ group. That is encouraging.

 

March 22nd & 23rd, 2020

  • “BCG may also increase the ability of the immune system to fight off pathogens other than the TB bacterium, according to clinical and observational studies published over several decades by Danish researchers Peter Aaby and Christine Stabell Benn, who live and work in Guinea-Bissau. They concluded the vaccine prevents about 30% of infections with any known pathogen, including viruses, in the first year after it’s given.“
  • “One small study reported that hydroxychloroquine alone or in combination with azithromycin reduced detection of SARS-CoV-2 RNA in upper respiratory tract specimens compared with a non-randomized control group but did not assess clinical benefit [7].“
  • A lost sense of smell?
  • (NYTimes) There is growing anecdotal evidence that anosmia — loss of the sense of smell — is an indicator of a Covid-19 infection.
  • New York State (ref):
  • “Acquires 70,000 Doses of Hydroxychloroquine, 10,000 doses of Zithromax and 750,000 Doses of Chloroquine to Implement Drug Trials - Trials Will Start Tuesday [March 24, 2020]”
  • Zithromax is the same as Azithromycin above
  • CQ, hCQ, Kaltra, and Remdesivir.

March 20th & March 21st, 2020

  • “Scientists are rushing to estimate the proportion of people with mild or no symptoms who could be spreading the pathogen.”
  • “by 18 February, there were 37,400 people with the virus in Wuhan whom authorities didn’t know about.”
  • “By our most conservative estimate, at least 59% of the infected individuals were out and about, without being tested and potentially infecting others,” says Wu Tangchun, a public-health expert at Huazhong University of Science and Technology in Wuhan, who led the study. “This may explain why the virus spread so quickly in Hubei and is now circulating around the world.”
  • “suspects the rate of asymptomatic infections in a general population might be closer to the 31%....Taking the results from several studies into account, Chowell thinks that asymptomatic or mild cases combined represent about 40–50% of all infections.”
  • “But can people with mild or no symptoms infect others?”
  • In addition to the German study that I wrote about in the “contagious” section → “Another team, in China, detected high viral loads in 17 people with COVID-19 soon after they became ill. Moreover, another infected individual never developed symptoms but shed a similar amount of virus to those who did, the researchers report5 yesterday in The New England Journal of Medicine.”
  • Added to the “what should I do” section:

March 18th & March 19th, 2020

The volume of new information is coming in at a pace that is unsustainable to keep up with and also maintain a day job, so I’ll describe the highlights that stood out to me (roughly in reverse chronological order, and I’m sure I missed a ton):

  • Three of the best places to learn about what’s going on at a more scientific level include Nature, Science, and Stat News.
  • I enjoyed reading this highly controversial article in Stat News by JOHN P.A. IOANNIDIS entitled “A fiasco in the making? As the coronavirus pandemic takes hold, we are making decisions without reliable data”
  • I think it’s important to read articles a bit outside of mainstream consensensus, especially if the author is using logic and data (or pointing out the lack thereof) to make a point.
  • Very much complementary to Ioannidis’ article above, Gretchen Vogel wrote a compelling article in Science about the importance of blood tests that detect COVID-19 antibodies
  • “Florian Krammer, a virologist at the Icahn School of Medicine at Mount Sinai, and his colleagues posted a preprint yesterday describing a SARS-CoV-2 antibody test they have developed, and directions for replicating it.”   
  • “Widespread antibody testing could also provide key data for efforts to model the course of the pandemic. Current predictions vary so widely, causing some scientists to question the need for severe containment methods such as lockdowns and social distancing. By indicating how much of the population is already immune because of mild infections, antibody data could offer a key to how fast the virus will continue to spread.”
  • My own thoughts/commentary on this:
  • It’s fascinating to think that many of us have already had COVID-19 and have developed antibodies to it.  It seems like this is something we should all know.
  • Interestingly, and this is lost in headlines and the current frenzy, all of us have had (many) coronaviruses in the past, as they cause the common cold.
  • There’s plenty of data to prove that many who are infected with SARS-CoV-2 display only mild symptoms, albeit COVID-19 is certainly distinct from the common cold (e.g. a “runny nose” and upper respiratory congestion is apparently rare w/ COVID-19).
  • Vogel’s article above also made this fascinating point (hypotheses by scientists), although we don’t (yet) have evidence to suggest this is going on with SARS-CoV-2, as antibodies to NL63 (e.g. common cold), for example, don’t react to SARS-CoV-2:
  • “Existing antibodies can react to the related invader and trigger a dangerous overreaction, a phenomenon known as an antibody-dependent enhancement (ADE). Some researchers have suggested ADE might explain why the virus is more deadly in the elderly and less so in children, who have had less exposure to other coronaviruses.”
  • Do people develop immunity?
  • If humans do develop immunity, how long does it last?
  • What kind of immune response should vaccine developers look for?
  • How do we know if a vaccine is likely to work?
  • Will it be safe?
  • I thought Bill Gates’ response was appropriate

  • “Genomic analyses of the new coronavirus have revealed that its spike protein differs from those of close relatives, and suggest that the protein has a site on it which is activated by a host-cell enzyme called furin.”
  • “furin is found in lots of human tissues, including the lungs, liver and small intestines, which means that the virus has the potential to attack multiple organs, says Li Hua, a structural biologist at Huazhong University of Science and Technology in Wuhan, China, where the outbreak began. The finding could explain some of the symptoms observed in people with the coronavirus, such as liver failure”

March 13th, 2020 through March 17th, 2020

With a massive amount of new information coming in, the US (finally) taking social isolation seriously, and my family/friends asking me about my COVID-19 research and daily learnings, I launched http://www.covid19science.info and included multiple iterations/updates from my original article from March 12th.

On Sunday March 15th, my colleagues and I (and significant others) from around the world had a zoom meeting to have a frank discussion about COVID-19 and its impact on our personal and professional lives. One person on the call had just been tested that morning (it came back negative the next day). Another person was involved in the front lines of a hospital system in the US (in a hot zone) and was able to give us valuable information about the state of affairs outside the news we were hearing.

Early March through March 13th, 2020

This is when I and many others in the broader US community began studying COVID-19 in earnest. On March 12th I published the first version of my article on COVID-19 science, entitled “Coronavirus Disease 2019 (COVID-19): Understanding the epidemiology, biochemistry, and cognitive biases regarding the spread of — and our reaction to — SARS-CoV-2”

This was an excuse to both learn about the underlying science myself (including vaccines and antivirals), and an opportunity to study the wide variety of cognitive biases that I and many others were succumbing to when considering how to respond to COVID-19.  

Early March, 2020

People in WA and elsewhere in the USA started taking social isolation seriously. When I was in Seattle for meetings on March 2nd, for example, many were avoiding handshakes, getting too close, etc... Public places were still open, but thin on human attendance.

February 2020

Obviously things started to get a lot more serious, and by the end of the month we had our first death from COVID-19 in WA state (where I live most of the year).

January 2020

This is when I (and many from the western world) became aware of the novel (new) virus. I listened to a podcast from A16z that made me realize this was going to be a problem.  

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Author’s note: thanks for reading. Head over to my subscribe page and sign up for topics (like COVID-19) that interest you, and I hope to hear from you over social (I’m @wclittle in most places), email (will@wclittle.com), or future comment threads we’ll have on this site. Thanks!  

Topics: Health Science COVID-19
Will Little Subscribe

Managing Director at Prota Ventures.
I'm a bioengineer-turned-software-developer and venture builder/investor. Learn more about me professionally on LinkedIn, personally here, and check out the podcast I host, Ventures.